Brain and Development

Editorial Board

2009-11-01

Evaluation of serum lipids and carotid artery intima media thickness in epileptic children treated with valproic acid

2008-12-09

Abstract: The aim of this study is to evaluate the carotid artery intima media thickness and serum lipids in pediatric patients with epilepsy treated with valproic acid. The study included 44 pediatric epileptic and 40 healthy children. Intima media thickness of left common carotid artery and fasting lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) were assessed. Although we did not observe any differences regarding serum lipid profiles, intima media thickness of common carotid artery was significantly higher in epileptic patients treated with valproic acid. We suggest that this increase in intima media thickness of common carotid artery may be due to epilepsy and/or valproic acid treatment.

Intracerebral cell transplantation therapy for murine GM1 gangliosidosis

2009-01-05

Abstract: We performed a cell transplantation study to treat the brain involvement in lysosomal storage diseases. We used acid β-galactosidase knock-out mice (BKO) from C57BL/6 as recipients. To minimize immune responses, we used cells derived from transgenic mice of C57BL/6 overexpressing the normal human β-galactosidase. Fetal brain cells (FBC), bone marrow-derived mesenchymal stem cells (MSC), and mixed FBC and MSC cells were prepared and injected into the ventricle of newborn BKO mouse brain. The mice were examined at 1, 2, 4, and 8 weeks and 6 months after injection. In each experiment, the injected cells migrated into the whole brain effectively and survived for at least 8 weeks. Decrease in ganglioside GM1 level was also observed. FBC could survive for 6 months in recipient brain. However, the number of transplanted FBC decreased. In the brains of MSC- or mixed cell-treated mice, no grafted cells could be found at 6 months. To achieve sufficient long-term effects on the brain, a method of steering the immune response away from cytotoxic responses or of inducing tolerance to the products of therapeutic genes must be developed.

No differences in MR-based volumetry between 2- and 7-year-old children with autism spectrum disorder and developmental delay

2008-12-10

Abstract: Objective: To study brain volumes in children with ASD as compared to children with a mental retardation or a language delay (developmentally delayed). In addition, to study the association of intellectual functioning on brain volumes in children with ASD or developmental delay. Methods: Thirty-four children with ASD and 13 developmentally delayed children without ASD, between 2 and 7 years old, matched on age and developmental level, participated in a MRI study. Volumes of cranium, total brain, cerebellum, grey and white matter, ventricles, hippocampus and amygdala were measured. Results: No significant differences in volumes of intracranium, total brain, ventricles, cerebellum, grey or white matter or amygdala and hippocampus between the ASD group and the developmentally delayed group were found. In the developmentally delayed group, a significant correlation (0.73) was found between intellectual functioning and total brain volume after partialling out intracranial volume. In the ASD group, the correlation between intellectual functioning and brain volume corrected for intracranial volume was not significant. Conclusion: No evidence was found for overall differences in brain volumes in children with ASD compared to developmentally delayed children between 2 and 7 years. The finding that higher intellectual functioning was not associated with a relative larger brain volume in children with ASD may suggest that a relative enlargement of the brain may not be beneficial to patients with autism.

Serum and cerebrospinal fluid levels of cytokines in acute encephalopathy associated with human herpesvirus-6 infection

2008-12-29

Abstract: Human herpesvirus-6 (HHV-6) is a causative agent of exanthema subitum. The immunological pathogenesis of acute encephalopathy associated with HHV-6 infection is still unclear. We measured the concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in serum and cerebrospinal fluid (CSF) during the acute stage in 15 infants with acute encephalopathy and 12 with febrile seizures associated with HHV-6 infection. The serum IL-6, IL-10, sTNFR1, CSF IL-6, and sTNFR1 levels of infants with encephalopathy who had neurological sequelae (n=9) were significantly higher than those with febrile seizures (p=0.011, 0.043, 0.002, 0.029, and 0.005, respectively). In acute encephalopathy, serum IL-6, sTNFR1, and CSF IL-6 levels in infants with neurological sequelae were significantly higher than those without (n=6) neurological sequelae (p=0.043, 0.026, and 0.029, respectively), and serum IFN-γ, IL-6, IL-10, and sTNFR1 levels were significantly higher than those in the CSF (p=0.037, 0.037, 0.001, and 0.021, respectively). There were no significant differences in serum or CSF cytokine levels between infants who were positive for HHV-6 DNA in the CSF (n=6) compared to those who were negative (n=9). We suggest that cytokines mediate the pathogenesis of acute encephalopathy associated with HHV-6 infection, and that the elevated levels of serum IL-6, sTNFR1, and CSF IL-6 are important for predicting neurological sequelae.

A pilot study on the changes in immunity after ACTH therapy in patients with West syndrome

2009-01-05

Abstract: Adrenocorticotropic hormone (ACTH) has been the first-line drug for the treatment of West syndrome, although the therapy has various adverse effects. ACTH depresses resistance to a variety of bacterial, viral, protozoal, and fungal agents. The timing of the various vaccinations is delayed after ACTH therapy in Japan, because the immune system is believed to be affected for approximately 6 months. However, the duration of the effect of ACTH on the immune system is not known. Therefore, we examined changes in the immunity levels before and after ACTH therapy. We measured white blood cell counts, lymphocyte counts, T/B cell counts, CD4+ and CD8+ T cell counts, CD 4/8 ratio, lymphocyte blastoid transformation by PHA or Con-A, and the levels of IgA, IgM, and IgG before, immediately after, and 1, 3, 6, and 12 months after ACTH therapy. The lymphocyte counts and CD4+ T cell counts were significantly decreased immediately after and at 1 and 3 months after the therapy, and did not return to the previous levels even at 6 months and 12 months after ACTH treatment; however, these levels returned to within normal limits (within the 95% confidence interval). Immunoglobulin levels did not change after the ACTH therapy. Helper T cells were more depressed than cytotoxic T cells after ACTH therapy.

Efficacy of buccal midazolam compared to intravenous diazepam in controlling convulsions in children: A randomized controlled trial

Bibek Talukdar, Biswaroop Chakrabarty — 2008-12-29

Abstract: A study was done to examine the efficacy of buccal midazolam in controlling convulsion in children by comparing it with intravenous diazepam, a standard mode of treating convulsions. One hundred and twenty cases presenting with convulsions to emergency were treated randomly with either buccal midazolam (in a dose of 0.2mg/kg) or intravenous diazepam (in a dose of 0.3mg/kg). Partial seizures, generalized tonic, clonic and tonic–clonic convulsions were included irrespective of duration or cause. One episode per child only was included. The frequency of overall control of convulsive episodes within 5min were 85% and 93.3% in buccal midazolam and intravenous diazepam groups, respectively; the difference was, however, not statistically significant (p=0.142). The mean time needed for controlling the convulsive episodes after administration of the drugs was significantly less with intravenous diazepam (p=<0.001). The mean time for initiation of treatment was significantly less with buccal midazolam (p=<0.001). The mean time for controlling the convulsive episodes after noticing these first were significantly less with buccal midazolam than with intravenous diazepam (p=0.004) that is likely to be due to longer time needed for initiating treatment with intravenous diazepam in preparing the injection and establishing an IV line. There was no significant side effect in both the groups. The findings suggest that buccal midazolam can be used as an alternative to intravenous diazepam especially when getting an IV line becomes difficult. In situations where establishing an IV line is a problem, buccal midazolam may be the first choice.

Developmental characteristics of visual cognitive function during childhood according to exploratory eye movements

2009-01-19

Abstract: To evaluate the development of visual cognitive function in childhood, we examined exploratory eye movements in 84 healthy subjects viewing picture-based stimuli. Age-defined groups included 4- to 6-year-olds, 7-year-olds, 10-year-olds, 14-year-olds, 16-year-olds, and adults. In each group, 7 subjects were male and 7 were female. Exploratory eye movements, recorded as gaze points using an eye-mark recorder, were analyzed in terms of the total number of gaze points (TNGP); total eye-scanning length of gaze points (TESL); total number of gaze points on the left (l TNGP) and right (r TNGP) of the screen; and responsive search score (RSS) on the left (l RSS) and right (r RSS) of the screen. Both the TESL and TNGP increased significantly with age. The TESL and TNGP of 16-year-olds and adults viewing a repeat-comparison figure were significantly greater than when viewing a comparison figure. During the repeat-comparisons, the TNGP in 4- to 6-year-olds was greater on the right than the left; the opposite was true in 16-year-olds and adults. The RSS in 4- to 10-year-olds was greater on the right than the left; 16-year-olds and adults showed the reverse findings. Thus, in the repeat-comparison task, TNGP, TESL, TNGP, and RSS differences between left and right visual fields are useful biologic markers for estimating the development of visual cognitive function.

Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome

2009-09-24

Abstract: Mutations of the gene encoding the α2 subunit of the neuronal sodium channel, SCN2A, have been found in benign familial neonatal-infantile seizures (BFNIS). In Dravet syndrome, only one nonsense mutation of SCN2A was identified, while hundreds of mutations were found in the paralogue gene, SCN1A, which encodes the α1 subunit. This study examines whether SCN2A mutations are associated with Dravet syndrome. We screened for mutations of SCN1A, SCN2A and GABRG2 (the gene encoding γ2 subunit of the GABAA receptor) in 59 patients with Dravet syndrome and found 29 SCN1A mutations and three missense SCN2A mutations. Among the three, one de novo SCN2A mutation (c.3935G>C: R1312T) identified in a patient was thought to affect an arginine residue in a voltage sensor of the channel and hence, to be pathogenic. This finding suggests that both nonsense mutations and missense SCN2A mutations cause Dravet syndrome.

Reversible uncal herniation in a neonate with a large MCA infarct

Ronald L. Thibert, Joseph D. Burns, Rafeeque Bhadelia, Masanori Takeoka — 2008-12-19

Abstract: Uncal herniation due to a large cerebral infarct is well-described in adults, with high rates of morbidity and mortality. This phenomenon, however, has not been previously reported in neonates. We present a newborn male delivered via cesarean section with difficult extraction who presented with frequent seizures. He was found to have an acute left MCA territory infarct secondary to an M1 occlusion detected on MRI/MRA. He became lethargic and developed a left uncal herniation on CT at 72h of life. He was treated medically with osmolar agents and hemodynamic support, and had resolution of the herniation on CT at 120h of life. At 19 months he had residual moderate right hemiparesis with only mild gait disturbance and mild speech delay. As seen in this case, uncal herniation, though rare, may occur in neonates. Also, the outcome for this neonate was much better than for typical adults with a similar disease course.

Usefulness of single-channel amplitude-integrated electroencephalography for continuous seizure monitoring in infancy: A case report

2009-01-14

Abstract: We continuously monitored clustered seizures using single-channel amplitude-integrated electroencephalography (aEEG) in a 6-month-old girl with probable benign partial epilepsy in infancy (BPEI). The patient was admitted with clustered seizures, and aEEG using three disposable electrodes was started by a non-expert pediatrician. During the recording, seven seizures were detected. The last seizure was nearly overlooked on clinical observation, but was later confirmed on the basis of aEEG findings. The efficacy of antiepileptic drugs could also be objectively assessed from aEEG findings. Our results show that aEEG is useful for the continuous monitoring of seizures even in older children.

Growth disturbance of frontal lobe in BCECTS presenting with frontal dysfunction

Hideaki Kanemura, Masao Aihara — 2009-01-27

Abstract: A considerable proportion of children with benign childhood epilepsy with centrotemporal spikes (BCECTS) have increasingly been found to show neuropsychiatric deficits such as cognitive impairment and impulsivity, possibly associated with frontal lobe dysfunctions. We performed 3-dimensional magnetic resonance imaging (MRI)-based brain volumetry to characterize serial changes in frontal and prefrontal lobe volumes and compare volumetric changes with clinical symptoms. Serial changes in regional cerebral volumes were measured in a 5-year-old boy with BCECTS. Seizures were not easily controlled, and he demonstrated oromotor deficits, cognitive impairments and behavioral problems. Cognitive and behavioral deficits persisted even after remission of seizure disorder and oromotor deficits. Two BCECTS patients (5–6 years old) without neuropsychological disorders served as typical BCECTS, and nine normal subjects (4–10 years old) served as controls. Volumes of the frontal and prefrontal lobes were determined using a workstation, and prefrontal to frontal lobe volume ratio was calculated. Frontal and prefrontal lobe volumes showed no growth even after remission of seizure disorders. Prefrontal to frontal lobe volume ratio reduced slightly even after remission of both seizure disorders and EEG abnormalities. The result suggests that BCECTS presenting with atypical course may be associated with frontal lobe dysfunction resulting in cognitive and behavioral deficits.

A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy

2009-02-09

Abstract: Holocarboxylase synthetase (HCS) deficiency is an inborn error of biotin metabolism, leading to a multiple carboxylases deficiency. As the affected fetus sometimes presents with enlargement of the cerebral ventricles and intrauterine growth retardation (IUGR), prenatal administration of biotin has been attempted in some pregnancies. We present herein the case of a Japanese neonate with HCS deficiency who received maternal administration of biotin (10mg/day) from 33 weeks’ gestation. After biotin administration, the fetal body weight increased and gestation was continued to full term. However, lactic acidemia and metabolic acidosis were observed after birth. To evaluate the effects of prenatal therapy, we collected serum samples and measured the acylcarnitine profiles using high-performance liquid chromatography electrospray ionization tandem mass spectrometry. At birth, levels of propionylcarnitine and 3-hydroxyisovalerylcarnitine had already increased. At 2h after birth, these levels of acylcarnitines were further increased. At 3.5h after the start of biotin, these chemical findings were slightly improved. In conclusion, we considered that prenatal biotin therapy at 10mg/day may have been inadequate to avoid neonatal acidotic crisis in this case.

A case of carbamoyl phosphate synthetase 1 deficiency presenting symptoms at one month of age

2009-01-27

Abstract: Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is an autosomal recessive disorder of the urea cycle which causes hyperammonemia. Two forms of CPS1D are recognized: a lethal neonatal type and a less severe, delayed onset type. Neonatal CPS1D cases often present their symptoms within the first days of life. Delayed onset type were adolescents or adults, and infantile cases were rare. We report a case of CPS1D in a boy who developed symptoms at one month of age. He showed excellent response to treatments including continuous hemodialysis, drugs and a low-protein diet. His development and weight gain were good at the last follow-up at 1 year and three months of age. Molecular assay of the CPS1 gene demonstrated that the patient was heterozygous for c.2407C>G (R803G: maternal) in exon 20 and c.3784C>T (R1262X: paternal) in exon 32. Our clinical experience suggests that CPS1D could be one of the causes of hyperammonemia in early infantile cases.

Salmonella encephalopathy successfully treated with high-dose methylpredonisolone therapy

Kazushi Ichikawa, Akiko Kajitani, Akiko Tsutsumi, Saoko Takeshita — 2009-02-12

Abstract: We present a 7-year-old boy diagnosed as having salmonella encephalopathy. He developed severe consciousness disturbance following enterocolitis. Electroencephalography showed diffuse and high-voltage slow activity but MR images of the brain were normal. Examination of inflammatory cytokines in serum and cerebrospinal fluid revealed high levels of interleukin-6, -8, and -10, and interferon gamma. Salmonella typhimurium was detected in a stool specimen. He was diagnosed as having salmonella-associated encephalopathy that had features of septic encephalopathy and quickly responded to high-dose methylpredonisolone therapy. High-dose methylpredonisolone was considered to be an effective treatment for hypercytokine-mediated S. encephalopathy.

Corrigendum to “Programmed cell death in the lithium pilocarpine model: Evidence for NMDA receptor and ceramide-mediated mechanisms” [Brain Dev 30 (2008) 513–519]

2009-09-01

The authors regret that in the above article, the surname of the 8th author was incorrect. The correct list of authors is printed above.

Volume Contents

2009-11-01

Author Index

2009-11-01

Subject Index

2009-11-01

Announcements and reports

2009-11-01